RESUMO
Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.
RESUMO
BACKGROUND: Non-adherence to medication is a challenging problem in daily clinical practice. OBJECTIVE: To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. METHODS: ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. RESULTS: The DACH cohort had significantly different levels of adherence depending on the IMID (P < 0.05) and the type of therapy (P < 0.05). Based on the significant influence of concerns on treatment adherence (P < 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. CONCLUSIONS: In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups.
Assuntos
Artrite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação/psicologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Áustria , Estudos Transversais , Fármacos Dermatológicos/uso terapêutico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Espondilite Anquilosante/tratamento farmacológico , Inquéritos e Questionários , Suíça , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: Several treatment options are currently available for the treatment of psoriasis. OBJECTIVE: To explore the main associations between patients' characteristics and systemic treatments prescribed for psoriasis in a large group of patients observed in real-life clinical practice. METHODS: This was a retrospective analysis of baseline data collected within the Swiss Dermatology Network for Targeted Therapies registry in Switzerland between March 2011 and December 2017. Semantic map analysis was used in order to capture the best associations between variables taking into account other covariates in the system. RESULTS: A total of 549 patients (mean age 46.7 ± 14.7 years) were included in the analysis. Conventional therapies such as retinoids and methotrexate were associated with no previous systemic therapies for psoriasis, a moderate quality of life (QoL) at therapy onset and older age (≥60 years). Fumaric acid derivatives were associated with mild psoriasis (psoriasis area severity index < 10) and long disease duration (≥20 years). On the other side, cyclosporine and psoralen and ultraviolet A/ultraviolet B treatments were linked to a more severe condition, including impaired QoL, hospitalization and inability to work. Regarding biological therapies, both infliximab and adalimumab were connected to the presence of psoriatic arthritis, severe disease condition and other comorbidities, including chronic liver or kidney diseases and tuberculosis. Etanercept, ustekinumab and secukinumab were all connected to a complex history of previous systemic treatments for psoriasis, moderate disease condition, overweight and university education. CONCLUSIONS: The analysis shows multifaceted associations between patients' characteristics, comorbidities, disease severity and systemic treatments prescribed for psoriasis. In particular, our semantic map indicates that comorbidities play a central role in decision-making of systemic treatments usage for psoriasis. Future studies should further investigate specific connections emerging from our data.
Assuntos
Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/fisiopatologia , Sistema de Registros , SuíçaRESUMO
SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare disease with inflammatory osteoarticular and skin involvement. The pathogenesis of SAPHO syndrome remains unclear, but evidence suggests it may be an autoinflammatory disease triggered upon exposure to infectious agents in genetically predisposed individuals. Induction of the interleukin (IL)-23/T helper 17 axis in addition to neutrophil activation seem to play a key role, and therapies targeting these immunological pathways, including tumour necrosis factor (TNF) inhibitors, ustekinumab, secukinumab and the IL-1 inhibitor anakinra, are potential treatment options that need further investigation. Here we report a case of a 24-year-old woman with SAPHO syndrome who presented at our clinic with palmoplantar pustulosis and sternoclavicular joint involvement. Previous treatments with topical steroids and keratolytics combined with nonsteroidal anti-inflammatory drugs, intravenous methylprednisolone, methotrexate and sulfasalazine had all failed to improve symptoms. Therapy with etanercept was not tolerated, and because of a previous demyelinating peripheral neuropathy, further treatment with TNF inhibitors was avoided. We initiated ustekinumab 45 mg, which improved skin manifestations but not joint pain. Dose escalation to 90 mg initially improved joint pain, but the dose had to be reduced to 45 mg again because of increased infections. During subsequent 45-mg ustekinumab treatment, joint pain exacerbated so we switched to adalimumab which caused an exacerbation of the disease, so we switched to secukinumab, which improved skin and joint symptoms significantly but was associated with a pustular hypersensitivity reaction. Finally, we began treatment with apremilast, a pan-cytokine approach, resulting in stabilization of the skin and joint symptoms without side-effects. To our knowledge, this is the first case report of apremilast as a treatment for SAPHO syndrome.
Assuntos
Síndrome de Hiperostose Adquirida/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Talidomida/análogos & derivados , Síndrome de Hiperostose Adquirida/patologia , Adulto , Resistência a Medicamentos , Feminino , Humanos , Talidomida/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
Here we report the case of a patient with psoriasis who developed ulcerative colitis most likely caused by adalimumab. After cessation of adalimumab, colitis improved significantly. However, as psoriasis worsened, the patient was switched to ustekinumab, which resulted in complete cessation of colitis. During the 2-year follow-up under ustekinumab therapy, no further gastrointestinal complaints occurred. Paradoxical psoriasis manifestations in inflammatory bowel disease (IBD) under tumour necrosis factor (TNF)-inhibitor therapy have been reported and paradoxical IBD occurred rarely (mostly Crohn disease) in patients with rheumatological conditions treated with infliximab or etanercept. Due to the highly probable association of adalimumab with the onset of colitis in this case, we would like to suggest the term 'paradoxical ulcerative colitis' (PUC) for this as yet extremely rarely reported phenomenon. To the best of our knowledge this is the first description of PUC in a patient with psoriasis and in adalimumab treatment. Our observation suggests that ustekinumab is an effective treatment option in patients with paradoxical anti-TNF-driven inflammatory reactions like psoriasis or IBD.
Assuntos
Adalimumab/efeitos adversos , Colite Ulcerativa/induzido quimicamente , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Administração Cutânea , Fármacos Dermatológicos/efeitos adversos , Esquema de Medicação , Substituição de Medicamentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids. OBJECTIVES: To determine whether canakinumab is an effective and safe treatment in PG. METHODS: Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least -1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels. RESULTS: Interleukin (IL)-1ß and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other. CONCLUSIONS: Our data indicate that IL-1ß plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Pioderma Gangrenoso/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Anticorpos Monoclonais Humanizados , Citocinas/metabolismo , Esquema de Medicação , Resistência a Medicamentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Pioderma Gangrenoso/metabolismo , Esteroides/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Biologics are used increasingly to treat moderate-to-severe psoriasis. Here the topical treatment habits (corticosteroids and vitamin D derivates) and moisturizer use of 97 Swiss patients (male 65, female 32) receiving adalimumab have been evaluated. METHODS: Using a short cross-sectional survey the pharmacist asked patients during telephone contact about their topical treatment habits and psoriasis activity. RESULTS: 47 patients with adalimumab monotherapy were still free of psoriatic lesions after a longer follow-up of 13 months of therapy; 8 of them still used topical treatment. In contrast, 38 of 50 patients with remaining lesions used topicals. More than 75% of patients indicated that the perceived efficacy of additional topical therapy was ≥5 on a visual analog scale (0-10). The use of moisturizers did not correlate with disease activity. CONCLUSION: Topical treatment use by adalimumab patients is associated with remaining disease activity. 83% of patients without residual plaques (40% of all adalimumab patients) are able to stop topical treatment completely.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Adalimumab , Administração Tópica , Corticosteroides/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Hábitos , Humanos , Masculino , Pessoa de Meia-Idade , Retinoides/uso terapêutico , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Scleromyxedema is a rare connective tissue disease that may affect numerous internal organs in addition to the skin. The disease is almost exclusively associated with monoclonal gammopathy. MATERIAL AND METHODS: This retrospective study summarizes the clinical characteristics of four patients with scleromyxedema. In all of the patients a systematic serological and apparative check-up was performed. RESULTS: The mean age of the four patients (three women and one man) was 51 years. In all cases, monoclonal gammopathy (3 cases of IgG lambda and 1 case of IgG kappa) was involved. In one patient, skin lesions were restricted to the upper part of the body and three patients had generalized disease. The internal organs of all patients were affected with fibrosis of the lungs, myositis and arthritis, peripheral polyneuropathy and hypomotility of the esophagus. The most effective forms of treatment in this patient collective were dexamethasone-pulse therapy, intravenous immunoglobulins and bortezomib. All patients had recurrences after finishing therapy. The mean observation period after the initial diagnosis of scleromyxedena was 6.25 years (range 2-11 years). CONCLUSION: Scleromyxedema is a rare multisystemic disease. The heterogeneous affection of internal organs necessitates a comprehensive check-up. The response to recently published treatment strategies is low and recurrences after finishing therapy are frequent.
Assuntos
Anti-Inflamatórios/uso terapêutico , Escleromixedema/diagnóstico , Escleromixedema/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Neutrophils are the first nonresident effector immune cells that migrate to a site of infection or inflammation; however, improper control of neutrophil responses can cause considerable tissue damage. Here, we found that neutrophil responses in inflamed or infected skin were regulated by CCR7-dependent migration and phagocytosis of neutrophils in draining lymph nodes (dLNs). In mouse models of Toll-like receptor-induced skin inflammation and cutaneous Staphylococcus aureus infection, neutrophils migrated from the skin to the dLNs via lymphatic vessels in a CCR7-mediated manner. In the dLNs, these neutrophils were phagocytosed by lymph node-resident type 1 and type 2 conventional dendritic cells. CCR7 up-regulation on neutrophils was a conserved mechanism across different tissues and was induced by a broad range of microbial stimuli. In the context of cutaneous immune responses, disruption of CCR7 interactions by selective CCR7 deficiency of neutrophils resulted in increased antistaphylococcal immunity and aggravated skin inflammation. Thus, neutrophil homing to and clearance in skin-dLNs affects cutaneous immunity versus pathology.